![]() Observed toxicities will be summarized, for all dose levels, in terms of type (organ affected or laboratory determination), severity, time of onset, duration, serum concentration of the active leflunomide metabolite, probable association with the study treatment and reversibility or outcome. Incidence of toxicity, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 After completion of study treatment, patients are followed up at 30 days and then every 28 days until disease progression (active follow-up) or every 3 months (long term follow-up). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive leflunomide orally (PO) once daily (QD) on days 1-28. OUTLINE: This is a dose-escalation study. To generate a preliminary ribonucleic acid (RNA)/microRNA (miRNA) and deoxyribonucleic acid (DNA) methylation signature associated with response of MM cells to leflunomide in vivo (mRNA/miRNA and DNA methylation, phase II only) and teriflunomide ex vivo (messenger RNA /miRNA). To explore the potential additive or synergistic effects of combining leflunomide with other classes of Food and Drug Administration (FDA)-approved drugs. To explore the ex vivo cytotoxicity of leflunomide toward primary multiple myeloma (MM) cells, in order to evaluate whether individual ex vivo leflunomide response might be a useful predictor of therapeutic response. To explore the relationship between polymorphisms in the CYP1A2, CYP2C19, or DHODH genes and toxicity/response. To assess the relationship between serum concentration of the active leflunomide metabolite, teriflunomide (A77 1726), and disease response. To characterize the relationship between serum concentration of the active leflunomide metabolite, teriflunomide (A77 1726), and toxicity. ![]() To obtain estimates of: response duration, clinical benefit response, overall survival, progression-free survival. To evaluate the anti-myeloma activity of leflunomide, when given as a single agent, as assessed by overall response rate (ORR). To assess the safety and tolerability of leflunomide at each dose level by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. ![]() To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of leflunomide, when given as a single agent. Leflunomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. ![]() This phase I/II trial studies the side effects and best dose of leflunomide in treating patients with multiple myeloma that has come back (relapsed) or has not responded to previous treatment (refractory). ![]()
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